PLATELET AND PLASMA THROMBOXANE A(2) IN E. COLI ENDOTOXIN SHOCK (ENDOTOXIN SHOCK, SEPTIC SHOCK ESCHERICHIA).
Contributors: Rush University, College Of Nursing.
Published: 1985
Number of pages: 107
Subjects: Health Sciences, Nursing.
Description: Thromboxane A(,2) (TXA(,2)) levels are elevated during sepsis, however, the precise contribution of this prostaglandin to the development of shock and its primary source remain unclear. Since thrombocytopenia occurs during shock, and platelets make TXA(,2), platelets have been implicated as a potential source. The purpose of this project was to elucidate the contribution of TXA(,2) to shock after first establishing a rabbit endotoxin infusion model. Rises in TXA(,2), as measured by its stable metabolite TXB(,2), were profiled and various shock indicators were monitored. Effects of TXA(,2) on these shock manifestations were evaluated via pre-treatment with prostaglandin inhibitors (methylprednisolone, aspirin or imidazole). Finally, alterations in platelet activity were assessed and platelet TXA(,2) production was measured.

Endotoxin infusion (0.02 mg/kg/min/120 min) resulted in 67% mortality, thus assuring the model's suitability for the study of shock. Hypotension was initially observed at 90 minutes and persisted throughout the 120 minutes of the study. Plasma thromboxane levels initially peaked at 15-30 minutes, declined at 45 minutes, and peaked again at 120 minutes. Platelet and white blood cell counts were depressed by 15 minutes and at all subsequent observation points.

Pre-treatment with aspirin and imidazole blocked TXA(,2) production throughout the study, but neither drug ameliorated thrombocytopenia. Methylprednisolone suppressed TXA(,2) generation for the first 60 minutes of infusion and attenuated thrombocytopenia at all time points. All drugs failed to prevent the hypotension, hyperglycemia, acidosis or leukopenia which accompanied endotoxin infusion.

Platelets, isolated after 30 minutes of endotoxin infusion, did not differ from controls in their TXA(,2) production or aggregatory response to threshold stimulation with thrombin, arachidonic acid or platelet activating factor.

These findings indicate that thromboxane production is unrelated to hypotension, hyperglycemia, acidosis or leukopenia. The administration of TXA(,2) inhibitors failed to protect against thrombocytopenia, therefore, it appears that TXA(,2) is not the cause of thrombocytopenia. Correlation of the onset of thrombocytopenia with early rises in thromboxane suggests that activation of platelets with consequent release of TXA(,2) may account for the early rises in plasma TXB(,2) observed in this study.
Notes: Source: Dissertation Abstracts International, Volume: 46-01, Section: B, page: 0115.

Thesis (D.N.SC.)--RUSH UNIVERSITY, COLLEGE OF NURSING, 1985.

School code: 0591.